Lifehacker: You provide a really convincing portrait of caffeine as a much more complex substance than we usually give it credit for. Is it fair to say the caffeine is not so much an "upper" as an "upper enabler?" As in, it doesn't do anything to rev you up, necessarily, but it prevents your brain from putting out signals of tiredness, fatigue, maybe boredom? Is there another short synopsis you prefer?

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Stephen Braun: Right. Caffeine is an indirect stimulant, as opposed to, say, amphetamine which liberates dopamine, a directly stimulating neurotransmitter. By blocking adenosine receptors, caffeine allows the brain's own stimulating neurotransmitters (i.e. glutamate and dopamine) to do their thing with greater gusto and less restraint. Like taking the chaperons out of a high school dance or something. This fundamentally limits the "high" you can get with caffeine—you can only get "high" to the extent that your on-board stimulating neurotransmitters will let you. It also makes caffeine extremely safe (unless you can lay your hands on purified, powdered caffeine and decide to inject it or something crazy like that).

Lifehacker: You cite loads of research pointing to caffeine reaction being very individualized—reactions, tolerance and withdrawal effects included. You suggest caffeine users "become your own scientist and do your own research." What would be a good way to self-test for caffeine effects?

Stephen Braun: Yes, people's brains are as unique as their fingerprints—more so, actually. We can be very different "under the hood" and that means what seems like a heaven-sent dollop of pure joyous energy for one person can be another person's ticket to a jittery, panicky, hell. Most people, I think, self-titrate their dose...medical-speak for finding the dose that confers maximum benefit with minimal side effects. This applies to all drugs, alcohol, cannabis, nicotine and others included. For some people, this means zero caffeine is best—it either doesn't do much for them or the side effects don't outweigh the bennies. Other folks stabilize at a dose that would evoke seizures in small mammals. Although I think most people conduct their "experiments" casually as part of growing up, learning more about caffeine (and other drugs) helps. For one thing, you understand that the brain will adjust itself to any drug—or try to—and that adjustment will change the effective dose. It'll also help if you want to scale back your consumption, which can be tough because the withdrawal symptoms can be miserable if you go too fast. So experiment, but experiment intelligently if you can.

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Lifehacker: Have you seen any smart suggestions on how to account for tolerance build-up? If you stick to a routine, it seems like the average coffee drinker can build a fairly complete tolerance after 10 days.

Stephen Braun: Tolerance is complicated. Yes, adenosine receptors in the brain clearly up-regulate in response to caffeine (by becoming more numerous, more sensitive, or both) and that means it'll generally take more caffeine, over time, to achieve the same degree of stimulation you felt after that first, virginal, mug of Joe (or whatever). But I don't think you ever achieve "complete" tolerance...even long-time coffee drinkers will still feel some kind of kick. Part of that, yes, is the hair-of-the-dog phenomenon...a long-time coffee drinker will feel better after the morning espresso in part because he or she is feeling the lethargy of caffeine withdrawal at that time of day and the caffeine brings them back to where they'd be if they'd never touched the stuff in the first place. But there is also some extra stimulation involved as the caffeine molecules overwhelm and plug up even the up-regulated adenosine receptors. There's only so much surface area on a neuron, after all!

In practical terms, this means that if you'd like to be able to turn to caffeine when you need it for a quick, effective jolt, it's best to let your brain "dry out" for at least several days prior to administration. This is actually my current mode of consumption. I don't regularly drink coffee anymore (gasp). This from a man who loved (and wore out) his home espresso maker. I love coffee in all its guises. But after 30+ years it wasn't working for me. For one thing, the problem with caffeine is that there are adenosine receptors all over the body, including muscles. For me, that meant that caffeine made me vaguely stiff and sore, and it aggravated a tender lower back that was prone to spasm. But I also just wasn't getting a clean, clear buzz from coffee...I drank so much, so regularly, that drinking an extra cup or two didn't do a helluva lot except, perhaps, make me a little more irritable. So about a year ago I slowly tapered down, and now I have, if anything, a cup of tea (half black, half peppermint) in the morning. (The amount of caffeine from the black tea isn't enough to wire a gnat.) Not only does my body feel better now, my brain is clean of caffeine, so I really want (or need) a good neural jump-start, I will freely...nay, ecstatically...indulge. Then I stop and let the brain settle again. That's the theory, anyway...and it's basically true, although I'll freely admit that sometimes I have an espresso or coffee just because it tastes so damned good.

Lifehacker: Have you seen any research, maybe newer than your book, into whether caffeine helps with memory, creative tasks, or, heck, email answering? Your book suggests that it all depends on the brain of the user—whether programming, for example, might be considered taxing or "play."

Stephen Braun: The research I'm familiar with clearly suggests that caffeine (at least initially) can enhance learning and memory, typically for so-called "declarative" memory (remembering lists of words, for example, or the kinds of things typically asked on exams). Creativity is another matter. There are different kinds of creativity and they may be best influenced by different types of molecules. Personally, I do tend to write more fluidly and with less effort under the influence of stimulants. But I suspect that for other types of creativity, such as in the visual or musical arts, cannabis would be a better tool. Or maybe both together!

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Lifehacker: Your book was written before the heavy marketing of giant, sugar-y, guarine-stuffed "energy drinks," which are now pretty much everywhere. Is there anything unique about Red Bull, Monster, etc. in terms of caffeine delivery or effect?

Stephen Braun: "Energy drinks" are just a new delivery vehicle for an ancient drug (and, as far as I know the amounts of caffeine contributed by the guarana, yerba mate, and other "herbs" is minimal—just a gimmick—the caffeine comes from the manufacture of decaf coffee). What is new with these, I think, is the way they are both marketed and used for simultaneous ingestion with alcohol. Of course, people have been mixing alcohol and caffeine for millenia, but, I suspect, not very deliberately. More like the alcohol at the end of a caffeine-fueled day or an espresso after the wine with dinner. With Red Bull and it's ilk, it seems the goal is truly simultaneous administration—which is much easier with these beverages because they're sweet and cold...perfect for pairing with vodka and other neutral spirits, if that's your pleasure. I'm inclined to suspect such mixing isn't a good thing. For one thing, you may end up drinking more than you would normally (and suffering the consequences, therefore) because you're jacked up on caffeine. For another, you'll be awake, but more intoxicated than you might realize, which could be very hazardous when mixed with driving or other machinery.

Lifehacker: What's the biggest or most wide-spread misunderstanding of caffeine?

Stephen Braun: Believe it or not, I think the biggest misunderstanding is the most basic: I don't think the mass of folks really consider caffeine a drug. It's so omni-present and, of course, so relatively mild and socially accepted, that I think, for the mass of people, it's almost invisible. Understanding caffeine as a drug can help make sense of things like rebound headaches, rebound fatigue, insomnia, or heightened anxiety—just some of the less pleasant things that can occur from caffeine consumption.